The present invention relates to a multifunctional reusable catalyst and to a process for the preparation thereof on a single matrix of the support to perform multicomponent reaction in a single pot. More particularly the present invention relates to preparation of multifunctional catalysts consisting of active palladium, tungsten and osmium species useful for the synthesis of chiral vicinal diols by tandem and/or simultaneous reactions involving Heck coupling, N-oxidation and AD reaction of olefins in presence of cinchona alkaloid compounds both as an native one and immobilized one in the said matrix support.
This invention also relates to a process for preparing vicinal diols by asymmetric dihydroxylation of olefins in presence of cinchona alkaloid compounds employing reusable multifunctional catalysts as heterogeneous catalysts in place of soluble osmium catalysts.
Products obtained by the dihydroxylation of olefins in presence of cinchona alkaloid compounds are important intermediates for the preparation of drugs and pharmaceuticals. For example the products of cinnamic acid esters are intermediates for taxol side chain. An anticancer drug, diltiazem, calcium antagonist and chloramphenicol can also be derived from the diols obtained through this method.
There are serious disadvantages in performing the catalytic AD reaction with homogeneous system in the manufacture of vicinal diols due to presence of toxic remnants of osmium in products and high cost of osmium tetroxide or potassium osmate dihydrate.
U.S. Pat. Nos. 4,871,855 and 5,260,421 disclose homogeneous asymmetric dihydroxylation of olefins by osmium tetroxide and cinchona alkaloids. The inherent disadvantages in this process are cumbersome procedure for the recovery of the osmium catalyst from the reaction mixture, generation of toxic waste and possibility of presence of toxic osmium in traces in the product.
U.S. Pat. No. 5,516,929 discloses heterogeneous asymmetric dihydroxylation of olefins by osmium tetroxide and polymer-bound cinchona alkaloids. The drawbacks of this process are the difficulty faced in quantitative recovery of toxic osmium catalyst, lower enantioselectivity and reduction in activity and enantioselectivity in each and every recycle experiments.
U.S. Pat. No. 5,968,867 discloses heterogeneous asymmetric dihydroxylation of olefins by osmium tetroxide and silica gel supported bis-cinchona alkaloid derivatives. The drawbacks are difficulty in quantitative recovery of toxic osmium catalyst and reduction in activity and enantioselectivity in each and every recycle experiments.
European patent EP 940,170 A2 discloses catalytic asymmetric dihydroxylation of alkenes using a polymer-supported osmium catalyst. The drawbacks are that higher amount of catalyst (5 mol %), longer reaction time and use of expensive polymer as a support are required.
Reference may be made to a publication J. Am. Chem. Soc. 2001, 123, 1365 wherein asymmetric dihydroxylation of olefins is done by osmium tetroxide and a biomimetic flavin in presence of cinchona alkaloids using H2O2 as oxidant under homogeneous conditions. The inherent disadvantages are difficulty in the recovery of osmium tetroxide and usage of unstable flavin.
The main object of the invention is to provide reusable multifunctional catalysts useful for the synthesis of chiral vicinal diols.
Another object of the invention is to prepare reusable multifunctional catalysts having transition metal elements such as palladium, osmium and tugsten deposited in a support having interstitial anions such as chloride, nitrate, carbonate, sulfate or calcined material.
Another object of the invention is to prepare reusable multifunctional catalysts on a single matrix of the support to perform multi-component reaction in a single pot.
It is another object of the invention to provide a novel and ecofriendly process for synthesis of chiral diols from aryl halides and olefins in a single pot.
It is another object of the invention to provide a process for the synthesis of chiral diols dispensing with the use of soluble and toxic osmium tetraoxide or potassium osmate dihydrate.
It is another object of the invention to provide a multifunctional catalysts are prepared and used as heterogeneous catalysts for synthesis of chiral diols which precludes the presence of osmium in traces with product.
It is another object of the invention to provide a process for the synthesis of chiral vicinal diols where enantioselectivity and the yields are good and work-up procedure simple.
It is another object of the invention to provide a process for the synthesis of chiral vicinal diols which is economical and environmentally safe without any disposal problem.
By employing the heterogeneous catalytic system, the cost naturally comes down due to easy recovery of the catalyst and very insignificant loss of osmium tetroxide, when compared with homogenous system. The products thus obtained using heterogeneous catalyst system are also benign since the presence of osmium in minor impurities in the dihydroxylated products is also precluded.
The present invention provides multifunctional catalysts consisting of palladium, osmium and tungsten species in their composition in its homogeneous or heterogeneous form through ion exchange or anchoring for the preparation of vicinal diols which are important intermediates for drugs and pharmaceuticals.
Accordingly the present invention relates to a reusable multifunctional catalyst useful for the preparation of chiral vicinal diols, the said catalyst having formula Sxe2x80x94M, wherein S is a support selected from the group consisting of LDH, resin, silica, clay alumina and Sxe2x80x2xe2x80x94NR3X wherein Sxe2x80x2 is a unmodified support selected from resin and silica, R is an alkyl group selected from the group consisting of methyl, ethyl, propyl and butyl, X is selected from the group consisting of Cl, Br, I, F, OH and OAc; and M is an active species comprising two or more different transition metals selected from the group consisting of palladium, ruthenium, osmium, tungsten, titanium, vanadium, chromium, manganese, iron, cobalt, nickel, copper, and molybdenum.
In one embodiment of the invention, the active species loading in the catalyst is in the range of 5 to 30% of support.
In another embodiment of the invention, the support as synthesized has an interstitial anion selected from the group consisting of chloride, nitrate, carbonate, sulfate, hydroxide and any mixture thereof.
In another embodiment of the invention, the reusable multifunctional catalyst prepared comprises of LDH-PdOs, resin-PdOs and SiO2xe2x80x94PdOs for the synthesis of chiral diols from aryl halides and olefins and SGS-(QN)2PHAL-PdOs for the preparation of chiral diols from aryl halides and olefins.
In another embodiment of the invention the reusable multifunctional catalyst prepared comprises of LDH-OsW, resin-OsW, SiO2xe2x80x94OsW, SGS-(QN)2PHAL-OsW and SGS-(QN)2PHAL-OsTi for the synthesis of chiral diols from olefins using H2O2.
In another embodiment of the invention the reusable multifunctional catalyst prepared comprises of LDH-PdOsW, resin-PdOsW, SiO2xe2x80x94PdOsW and SGS-(QN)2PHAL-PdOsW for the preparation of chiral diols from aryl halides and olefins using H2O2.
The present invention also relates to a process for the preparation of reusable multifunctional catalyst useful for the preparation of chiral vicinal diols, the said catalyst having formula Sxe2x80x94M, wherein S is a support selected from the group consisting of LDH, resin, silica, clay alumina and Sxe2x80x2xe2x80x94NR3X wherein Sxe2x80x2 is a unmodified support selected from resin and silica, R is an alkyl group selected from the group consisting of methyl, ethyl, propyl and butyl, X is selected from the group consisting of Cl, Br, I, F, OH and OAc; and M is an active species comprising two or more different transition metals selected from the group consisting of palladium, ruthenium, osmium, tungsten, titanium, vanadium, chromium, manganese, iron, cobalt, nickel, copper, and molybdenum said process comprising reacting salts of two or more said transition metals with said support in an aqueous solvent at a temperature ranging between 20 to 100xc2x0 C. for a period ranging from 5 to 24 h under nitrogen atmosphere followed by washing to obtain the desired reusable multifunctional catalyst.
In one embodiment of the invention, the active species loading in the catalyst is in the range of 5 to 30% of support.
In another embodiment of the invention, the support as synthesized has an interstitial anion selected from the group consisting of chloride, nitrate, carbonate, sulfate, hydroxide and any mixture thereof
In another embodiment of the invention, the reusable multifunctional catalyst prepared is selected from the group consisting of LDH-PdOs, resin-PdOs and SiO2xe2x80x94PdOs for the synthesis of chiral diols from aryl halides and olefins and SGS-(QN)2PHAL-PdOs for the preparation of chiral diols from aryl halides and olefins.
In another embodiment of the invention the reusable multifunctional catalyst prepared is selected from the group consisting of LDH-OsW, resin-OsW, SiO2xe2x80x94OsW, SGS-(QN)2PHAL-OsW and SGS-(QN)2PHAL-OsTi for the synthesis of chiral diols from olefins using H2O2.
In another embodiment of the invention the reusable multifunctional catalyst prepared is selected from the group consisting of LDH-PdOsW, resin-PdOsW, SiO2xe2x80x94PdOsW and SGS-(QN)2PHAL-PdOsW for the preparation of chiral diols from aryl halides and olefins using H2O2.
The present invention also relates to a process for the preparation of a chiral vicinal diol from aryl halide and olefin using a reusable multifunctional catalyst having formula Sxe2x80x94M, wherein S is a support selected from the group consisting of LDH resin, silica, clay, alumina and Sxe2x80x2xe2x80x94NR3X wherein Sxe2x80x2 is a unmodified support selected from resin and silica, R is an alkyl group selected from the group consisting of methyl, ethyl, propyl and butyl, X is selected from the group consisting of Cl, Br, I, F, OH and OAc; M is an active species comprising two different transition metals at least one of which is palladium and the other is selected from the group consisting of ruthenium, osmium, tungsten, titanium, vanadium, chromium, manganese, iron, cobalt, nickel, copper, and molybdenum, said process comprising reacting aryl halide and olefin using the said catalyst by Heck coupling and asymmetric dihydroxylation in the presence of an oxidant and a cinchona alkaloid compound in a solvent selected from the group consisting of water, acetone, acetonitrile and t-butanol, at a temperature in the range of xe2x88x9220 to 200xc2x0 C. for a period ranging from 0.5 to 48 hrs and obtaining the desired chiral vicinal diol.
In one embodiment of the invention, the quantity of multifunctional catalyst used in the reaction is in the range of 0.01 to 10 mol % of active species with respect to the substrate.
In one embodiment of the invention, the multifunctional catalyst used is recovered by filtration and is reused for several cycles with consistent activity.
In one embodiment of the invention, the oxidant used is selected from the group consisting of N-methyl morpholine N-oxide (NMO), trimethylamine N-oxide, hydrogen peroxide, t-butyl hydrogen peroxide, potassium ferricyanide, sodium periodate and molecular oxygen.
In one embodiment of the invention, the cinchona alkaloid compound used is selected from the group consisting of (DHQD)2PHAL, (DHQD)2PYR, (DHQD)2AQN, DHQD-OAc, DHQD-CLB, DHQD-PHN, DHQD-MEQ, DHQD-IND and other pseudoenantiomeric forms of such ligands.
The present invention also relates to a process for the preparation of chiral diol from aryl halide and olefin using a reusable multifunctional catalyst having formula Sxe2x80x94M, wherein S is a support selected from the group consisting of LDH, resin, silica, clay alumina and Sxe2x80x2xe2x80x94NR3X wherein Sxe2x80x2 is a unmodified support selected from resin and silica, R is an alkyl group selected from the group consisting of methyl, ethyl, propyl and butyl, X is selected from the group consisting of Cl, Br, I, F, OH and OAc; M is an active species comprising three different transition metals at least one of which is palladium and the other two are selected from the group consisting of ruthenium, osmium, tungsten, titanium, vanadium, chromium, manganese, iron, cobalt, nickel, copper, and molybdenum, the said process comprises reacting aryl halide and olefin using the said catalyst by Heck coupling, N-oxidation and asymmetric dihydroxylation in the presence of an oxidant and a cinchona alkaloid compound in a solvent selected from the group consisting of water, acetone, acetonitrile and t-butanol, at a temperature in the range of xe2x88x9220 to 200xc2x0 C. for a period ranging from 0.5 to 48 hrs and obtaining the desired chiral vicinal diol.
In one embodiment of the invention, the quantity of multifunctional catalyst used in the reaction is in the range of 0.01 to 10 mol % of active species with respect to the substrate.
In one embodiment of the invention, the multifunctional catalyst used is recovered by filtration and is reused for several cycles with consistent activity.
In one embodiment of the invention, the oxidant used is selected from the group consisting of N-methyl morpholine N-oxide (NMO), trimethylamine N-oxide, hydrogen peroxide, t-butyl hydrogen peroxide, potassium ferricyanide, sodium periodate and molecular oxygen.
In one embodiment of the invention, the cinchona alkaloid compound used is selected from the group consisting of (DHQD)2PHAL, (DHQD)2PYR, (DHQD)2AQN, DHQD-OAc, DHQD-CLB, DHQD-PHN, DHQD-MEQ, DHQD-IND and other pseudoenantiomeric forms of such ligands.
In yet another embodiment of the invention, the dihydroxylated chiral vicinal diols are important intermediates for the preparation of drugs and pharmaceuticals, products selected from taxol side chain, an anticancer drug, diltiazem, calcium antagonist and chloramphenicol, an antibiotic.
The present invention also relates to a process for the preparation of chiral diol from olefin using a reusable multifunctional catalyst having formula Sxe2x80x94M, wherein S is a support selected from the group consisting of LDH, resin, silica, clay, alumina and Sxe2x80x2xe2x80x94NR3X wherein Sxe2x80x2 is a unmodified support selected from resin and silica, R is an alkyl group selected from the group consisting of methyl, ethyl, propyl and butyl, X is selected from the group consisting of Cl, Br, I, F, OH and OAc; M is an active species comprising two different transition metals selected from the group consisting of ruthenium, osmium, tungsten, titanium, vanadium, chromium, manganese, iron, cobalt, nickel, copper, and molybdenum, the said process comprises dihydroxylating olefin using the said catalyst via N-oxidation in the presence of an oxidant and a cinchona alkaloid compound in a solvent selected from the group consisting of water, acetone, acetonitrile and t-butanol, at a temperature in the range of xe2x88x9220 to 200xc2x0 C. for a period ranging from 0.5 to 48 hrs and obtaining the desired chiral vicinal diol.
In one embodiment of the invention, the quantity of multifunctional catalyst used in the reaction is in the range of 0.01 to 10 mol % of active species with respect to the substrate.
In one embodiment of the invention, the multifunctional catalyst used is recovered by filtration and is reused for several cycles with consistent activity.
In one embodiment of the invention, the oxidant used is selected from the group consisting of N-methyl morpholine N-oxide (NMO), trimethylamine N-oxide, hydrogen peroxide, t-butyl hydrogen peroxide, potassium ferricyanide, sodium periodate and molecular oxygen.
In one embodiment of the invention, the cinchona alkaloid compound used is selected from the group consisting of (DHQD)2PHAL, (DHQD)2PYR, (DHQD)2AQN, DHQD-OAc, DHQD-CLB, DHQD-PHN, DHQD-MEQ, DHQD-IND and other pseudoenantiomeric forms of such ligands.
In yet another embodiment of the invention, the dihydroxylated chiral vicinal diols are important intermediates for the preparation of drugs and pharmaceuticals, products selected from taxol side chain, an anticancer drug, diltiazem, calcium antagonist and chloramphenicol, an antibiotic.
The novelty in the invention lies in the preparation of multifunctional catalysts through simple exchange process for the first time and use thereof in catalytic amounts for preparing vicinal diols by tandem and/or simultaneous reactions involving Heck coupling, N-oxidation and asymmetric dihydroxylation of olefins employing oxidants in presence of cinchona alkaloid compounds. Higher yields and enantioselectivities are obtained when multifunctional catalysts are used in the synthesis of diols. Since the dihydroxylated products are important intermediates for the preparation of drugs and pharmaceuticals, this invention that envisages reduction of toxic osmium metal content in these products is timely and appropriate. The consistent activity and enantioselectivity obtained for several cycles in multicomponent reaction makes the process economical and possible for commercial realization. Therefore, multifunctional catalysts are better option for the synthesis of vicinal diols. The use of different supports and varied compositions used in the preparation of multifunctional catalysts has no impact on its final form of catalysts with respect to activity and enantioselectivity. Thus this invention offers the best techno-economic route for the synthesis of chiral vicinal diols, intermediates for the preparation of drugs and pharmaceuticals.
Scientific Explanation
In the present invention, multifunctional catalysts have been synthesized for the first time and used in catalytic amounts for preparing vicinal diols by tandem and/or simultaneous reactions involving Heck coupling, N-oxidation and asymmetric dihydroxylation of olefins employing oxidants in presence of cinchona alkaloid compounds in a heterogeneous manner. Multifunctional catalysts are prepared by anion exchange of active species or anchoring through covalent bond formation on various supports originated from inorganic or organic. The metals immobilized on supports are responsible for the multifunctional activity of catalyst. The activity of heterogeneous multifunctional catalysts is similar or higher than the homogeneous counter parts. The higher activity is ascribed to the support effect. Higher yields and enantioselectivities are obtained with multifunctional catalysts used in the multicomponent reaction in aqueous organic solvents. Since the dihydroxylated products are important intermediates for the preparation of drugs and pharmaceuticals, this invention is timely and appropriate. Therefore, multifunctional catalysts are a better option for the synthesis of vicinal diols. The multifunctional catalysts prepared irrespective of support or method of immobilization used in the preparation of multifunctional catalysts offered good yields and enantioselectivies in presence of cinchona alkaloids.
Multifunctional catalysts are prepared and used in catalytic amounts for preparing vicinal diols by multicomponent reaction using oxidants in presence of cinchona alkaloid compounds in a heterogeneous manner are described in the following examples, which are by way of illustration and should not be construed to limit the scope of the invention.
Preparation of Multifunctional Catalysts